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| | ==Glutamate Racemase Mycobacterium tuberculosis (MurI) with bound D-glutamate, 2.3 Angstrom resolution, X-ray diffraction== | | ==Glutamate Racemase Mycobacterium tuberculosis (MurI) with bound D-glutamate, 2.3 Angstrom resolution, X-ray diffraction== |
| - | <StructureSection load='5hj7' size='340' side='right' caption='[[5hj7]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='5hj7' size='340' side='right'caption='[[5hj7]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hj7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HJ7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HJ7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hj7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HJ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HJ7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">murI, Rv1338, MTCY02B10.02, MTCY130.23 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamate_racemase Glutamate racemase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.1.3 5.1.1.3] </span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5hj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hj7 OCA], [https://pdbe.org/5hj7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hj7 RCSB], [https://www.ebi.ac.uk/pdbsum/5hj7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hj7 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hj7 OCA], [http://pdbe.org/5hj7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hj7 RCSB], [http://www.ebi.ac.uk/pdbsum/5hj7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hj7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MURI_MYCTU MURI_MYCTU]] Provides the (R)-glutamate required for cell wall biosynthesis. | + | [https://www.uniprot.org/uniprot/MURI_MYCTU MURI_MYCTU] Provides the (R)-glutamate required for cell wall biosynthesis. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Glutamate racemase (MurI) is responsible for providing D-glutamate for peptidoglycan biosynthesis in bacteria and has been a favoured target in pharmaceutical drug design efforts. It has recently been proven to be essential in Mycobacterium tuberculosis, the causative organism of tuberculosis, a disease for which new medications are urgently needed. In the present study, we have determined the protein crystal structures of MurI from both M. tuberculosis and Mycobacterium smegmatis in complex with D-glutamate to 2.3 A and 1.8 A resolution respectively. These structures are conserved, but reveal differences in their active site architecture compared with that of other MurI structures. Furthermore, compounds designed to target other glutamate racemases have been screened but do not inhibit mycobacterial MurI, suggesting that a new drug design effort will be needed to develop inhibitors. A new type of MurI dimer arrangement has been observed in both structures, and this arrangement becomes the third biological dimer geometry for MurI found to date. The mycobacterial MurI dimer is tightly associated, with a KD in the nanomolar range. The enzyme binds D- and L-glutamate specifically, but is inactive in solution unless the dimer interface is mutated. We created triple mutants of this interface in the M. smegmatis glutamate racemase (D26R/R105A/G194R or E) that have appreciable activity (kcat=0.056-0.160 min(-1) and KM=0.26-0.51 mM) and can be utilized to screen proposed antimicrobial candidates for inhibition.
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| - | Exploring the structure of glutamate racemase from Mycobacterium tuberculosis as a template for anti-mycobacterial drug discovery.,Poen S, Nakatani Y, Opel-Reading HK, Lasse M, Dobson RC, Krause KL Biochem J. 2016 May 1;473(9):1267-80. doi: 10.1042/BCJ20160186. Epub 2016 Mar 10. PMID:26964898<ref>PMID:26964898</ref>
| + | ==See Also== |
| - | | + | *[[Glutamate racemase 3D structures|Glutamate racemase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5hj7" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutamate racemase]] | + | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Krause, K]] | + | [[Category: Krause K]] |
| - | [[Category: Nakatani, Y]] | + | [[Category: Nakatani Y]] |
| - | [[Category: Poen, S]] | + | [[Category: Poen S]] |
| - | [[Category: Glutamate racemase tuberculosis drug design dimer kinetic]]
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| - | [[Category: Isomerase]]
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